Maternal Obesity Tied to Increased Risk of Colorectal Cancer in Offspring

By Linda Carroll

August 26, 2021

(Reuters Health) - Obesity in a pregnant woman may raise the risk of colorectal cancer in her child, a new study finds.

An analysis of data on 18,000 mother-child pairs from the Child Health and Development Studies (CHDS) reveals a more than two-fold increase in the risk of colorectal cancer in adults whose mothers were obese during pregnancy, according to the report published in Gut.

Among 68 cases of colorectal cancer in adult offspring, nearly half (48%) were diagnosed before age 50, the authors note.

"The most important thing we found is that early life events seem to be important risk factors for colorectal cancer," said the study's first author, Caitlin Murphy, an associate professor in the department of health promotion and behavioral sciences at the University of Texas Health Science Center's School of Public Health in Houston. "No one has been thinking about this. We showed that these events are important."

What sparked the study was the changing demographics of colorectal cancer.

"We, like many others, have been really alarmed at the rising rates of colorectal cancer in younger adults," Murphy said. "No one knows why. But when you see that the highest rates are in Gen X, that tells us that exposures in early life may be playing a role."

To take a closer look at whether maternal obesity might be implicated in colorectal cancer risk, Murphy and her colleagues analyzed data from the Child and Health Development Studies (CHDS) at the Public Health Institute in Oakland, California, which recruited nearly all (98%) pregnant women receiving prenatal care from the Kaiser Foundation Health Plan between June 1959 and September 1966.

A total of 18,751 live births were tracked through the CHDS to 14,507 mothers. At enrollment, the mothers supplied demographic and health-related information during in-person interviews. The researchers abstracted clinical information, including prenatal visits, diagnosed conditions and prescribed medication, from the mothers' medical records beginning six months prior to pregnancy through labor and delivery. Murphy and her team monitored CHDS participants by annual linkage to the California Department of Motor Vehicles, California Department of Vital Statistics, and the California Cancer Registry.

The researchers tracked incident diagnosis of colorectal cancer in adult offspring through 2019 by linkage with the California Cancer Registry, which is one of the largest cancer registries in the U.S.

During the study period, 68 offspring were diagnosed with colorectal cancer over 738,048 person-years of follow-up. Maternal obesity, defined as BMI of 30 or greater, was associated with an increase in colorectal cancer risk (adjusted hazard ratio 2.51) in the offspring. One in five offspring diagnosed with colorectal cancer during follow-up had a family history of colorectal cancer.

Total weight gain modified the association of rate of early weight gain in the offspring (relative excess risk due to interaction (RERI) −4.37), the authors note, suggesting discordant growth from early to late pregnancy increases risk. There was also an elevated association with birth weight greater than or equal to 4000 g (aHR 1.95), that did not achieve statistical significance.

One limitation of the study, the study team points out, is that the associations could be confounded by factors shared between mother and child, such as diet and microbiome, that were not measured in the CHDS. The study also didn't measure offspring BMI through adulthood.

The new study is "certainly thought provoking," said Dr. Michael Buckstein, a specialist in gastrointestinal cancers and an associate professor in the department of radiation oncology at the Icahn School of Medicine at Mount Sinai in New York City. "But I don't think it should worry mothers who have gained a lot of weight during pregnancy."

"Despite the fact that it uses a large anonymous database, it's fraught with problems," Dr. Buckstein said. "The fact that it has so many confounders and missing data deflates (some of the findings)."

One of the issues is that only a small proportion of the study participants have information on family history, Dr. Buckstein said. Another potential issue is that "presumably some of the exposures the child has in utero were probably there when the child was growing up," he added.

There's also no information on the weight of the person getting the cancer, which is obviously incredibly important," Dr. Buckstein said. "Not to mention the myriad of other factors (that can't be accounted for). It's a piece of the puzzle but certainly not everything."

This study suggests that exposures early in life - prenatally - can affect one's risk for colorectal cancer," said Frances Mary Modugno, an investigator at the Women's Cancer Research Center at the UPMC Hillman Cancer Center and the Magee-Women's Research Institute in Pittsburgh, Pennsylvania.

"In utero exposure has been associated with a host of health outcomes for the baby both in the short term and later in life," Modugno said in an email. "The association of maternal obesity with subsequent diagnosis of colon cancer in offspring, especially before the age of 50, suggests that something about the prenatal environment in obese and overweight women may influence colon cancer development in offspring. The take-home message here is that healthy weight maintenance in women desiring to have children is another way to contribute to the health and well-being of offspring."

The study just adds another reason to counsel prospective mothers to do their best to achieve a healthy BMI, Modugno said. "Counseling women intending to become pregnant on maintaining a healthy weight will support a healthier pregnancy and outcome for both the baby and mother," she added. "Reduced risk of colon cancer may be one such outcome for both the baby and mom!"

SOURCE: Gut, online August 24, 2021.